Abstract
Purpose
Immune checkpoint inhibitors (ICIs) are a promising option for the treatment of patients
with various cancers. Emerging case reports have raised awareness on hepatotoxicity,
a potentially fatal adverse event (AE) that may be associated with the use of ICIs.
This study assessed the potential association between ICIs and hepatotoxicity through
the mining of data from the US Food and Drug Administration's AE Reporting System
(FAERS).
Methods
A total of 9,217,181 AEs reported in the period from quarter 1 of 2004 to quarter
3 of 2021 were assessed. Information components (ICs) and reporting odds ratios (RORs)
were used to evaluate the association between the use of ICIs and hepatotoxicity.
Findings
A total of 52,463 AE reports listed ICIs, used alone or in combination, as a suspected
drug. Of these, 1481 cases were related to both ICIs and hepatotoxicity. The use of
ICIs was significantly associated with hepatotoxicity compared to all other drugs,
making it a safety signal (IC = 1.43 [95% CI, 1.36–1.51]; ROR = 2.78 [95% CI, 2.64–2.93]).
With monotherapy, all ICIs, except tremelimumab, were associated with liver damage.
The most commonly prescribed combination therapy was nivolumab + ipilimumab (321 cases)
with a significant signal detected. Notably, ICI use was significantly associated
with hepatic failure (IC = 1.24 [95% CI, 1.06–1.42]; ROR = 2.40 [95% CI, 2.13–2.72]).
The risk for ICI-associated hepatotoxicity (including hepatic failure) was greater
with ICI combination therapy than with ICI monotherapy. All subgroups by sex and age
also showed significant associations between ICI use and hepatotoxicity.
Implications
A significant association was detected between ICI use and hepatotoxicity. The risk
for hepatotoxicity (including hepatic failure) was greater with ICI combination therapy
compared with ICI monotherapy. (Clin Ther. 2023;45:XXX–XXX) © 2023 Elsevier Inc.
Key words
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Article info
Publication history
Published online: January 20, 2023
Accepted:
January 3,
2023
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 Published by Elsevier Inc.